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Role of the AE3 Chloride/Bicarbonate Exchanger in the Development of Cardiac Hypertrophy
Author(s) -
Sowah Daniel,
Alvarez Bernardo,
Shull Gary,
Casey Joseph
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.759.11
Subject(s) - medicine , endocrinology , muscle hypertrophy , angiotensin ii , chemistry , biology , receptor
Cardiac hypertrophy is one of the determinants of heart failure, the leading cause of hospitalization in the elderly in Western societies. Several factors contribute to the development of cardiac hypertrophy. Emerging evidence suggest that stimulation of the hypertrophic transport metabolon, a complex involving the Na + /H + exchanger, NHE1, carbonic anhydrase II and the AE3 Cl − /HCO 3 − exchanger, plays a key role in the development of hypertrophy. To understand the contribution of AE3 to the hypertrophic cascade, knock‐out mice lacking the gene that encodes AE3 (AE3 −/− ) were generated. The body weights showed no significant differences between the wild type (AE3 +/+ ), the heterozygous (AE3 +/–) and the knock‐out (AE3 −/− ) littermates. Interestingly, the heart weight to body weight ratio, an index of cardiac hypertrophy, was markedly reduced in the AE3 −/− mice (82 ± 2% vs. AE3 +/+ ); the AE3 +/− mice were identical to the AE3 +/+ mice (102 ± 3% vs. AE3 +/+ ). Phenylephrine (PE), 10 μM, or angiotensin II (ANG II), 1 μM, added 18 h following culturing of adult cardiomyocytes and present for 24 h, increased the cell size of isolated cardiomyocytes of AE3 +/+ mice by 20 ± 2% but AE3 −/− cardiomyocytes were unresponsive to PE‐ or ANG II‐induced hypertrophy (101 ± 4% vs. AE3 +/+ ). Our data demonstrate that deletion of the AE3 Cl − /HCO 3 − exchanger gene renders the myocardium significantly less sensitive to cardiomyocyte hypertrophy. Supported by the Heart and Stroke Foundation of Alberta.